To define differences between respiratory lesions induced by chemical carcinogens, infectious agents and vitamin A deficiency, we propose to compare cytokinetic and ultrastructural characteristics of squamous metaplasia in tracheobronchial epithelium of the hamster. The cytokinetic parameters will include labeling and mitotic indices, cell cycle parameters, growth fractions, and cell turnover times. Chemical carcinogens will be applied by multiple intratracheal instillations. Infections of the respiratory epithelium will be accomplished by intranasal or aerosol inoculation of Mycoplasma pulmonis or Sendai virus. Vitamin A deficiency will be induced by feeding ten- to 12-day pregnant hamsters on a 1:1 normal and vitamin A deficient diet. The litter will be maintained entirely on a vitamin A deficient diet until they are utilized. For measurements of different parameters, hamsters will be sacrificed at different intervals after application of the respiratory insults, and the tracheas processed for studying different parameters. Alterations in cytokinetic parameters will be studied by histochemical (Alcian blue-Period Acid Schiff's staining) and autoradiographic techniques. Ultrastructural and surface changes will be examined by transmission and scanning electron microscopes. Similar comparative studies will be carried out in vitro, since in contrast to the in vivo studies in which the effects of the test factors may be modified by the host's immune and inflammatory mechanisms, organ cultures of the trachea will provide a suitable tool for studying the induction and progression of squamous metaplasia by the above agents independently of host factors. For organ culture, tracheas will be cultured in CMRL 1066 medium supplemented with antibiotics, insulin, and hydrocortisone. Another important objective will be to study the above parameters associated with the inhibition and reversal of squamous metaplasia by retinoids.